First study of Ataxin-7 in fruit flies

Disruptive clumps of mutated protein are often blamed for clogging cells and interfering with brain function in patients with the neurodegenerative diseases known as spinocerebellar ataxias.

The protein clumps result from genes that develop a genetic “stutter” in which a three-letter segment of the DNA code is repeated over and over, leading to proteins containing long, redundant strings of a single amino acid called glutamine. These abnormal proteins are prone to aggregating with one another inside cells.

But a new study in fruit flies suggests that for at least one of these neurodegenerative diseases, the defective proteins may not need to form clumps to do harm. Researchers led by Investigators Jerry Workman, PhD, and Susan Abmayr, PhD, found a fruit fly version of Ataxin-7 which is mutated in patients with spinocerebellar ataxia type 7 (SCA7) disease. In humans, Ataxin-7 was known to aggregate in the cells of patients with SCA7 disease, but there was no direct evidence linking the aggregates to neurodegeneration.

The team found that fruit flies that lack Ataxin-7 experience neurodegeneration in the brain and the eye—paralleling the effects of the human disease. “The assumption has been that the disease is caused by the aggregated proteins,” Workman says. “But in the mutated fly, there’s no aggregated
protein. There’s no soluble protein. It’s not there at all. The lack of Ataxin-7 causes neurodegeneration in the fruit fly.”

“This sheds new light on what we think could be the cause of the SCA7 disease phenotype,” Abmayr says. The fruit fly has the potential to reveal more about Ataxin-7’s role in disease, say the scientists, who are now planning additional studies.

The study was published February 1, 2014, in the journal Genes & Development.